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Preliminary Study Of The Thrombomodulin N-terminal Domain’s Anti-inflammatory Effect

Posted on:2014-09-06Degree:MasterType:Thesis
Country:ChinaCandidate:N L ZhuFull Text:PDF
GTID:2254330422464297Subject:Infected subjects
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Objective:Thrombomodulin (TM) which is mainly secreted by vascular endothelial cellshas anti-inflammatory and anticoagulant effect through binding HMGB1, activatingprotein C, reducing the activity of thrombin. TM has three domain: EGF-like domain-anticoagulation by promoting the formation of protein C, others domains areN-terminal lectin-like domain (TM-N) and O-glycosylation–rich domain, whichfunction are not yet clear. Now we will have a basic research for TM-N. we set TM-N exist in different inflammatory response to find out the role and function of TM-Nand search it’s response mechanismMethods:LPS or HMGBI+LPS stimulated RAW264.7cells, then co-cultured with TM-N,detected the expression of IL–6mRNA、TNF-α、 IL-1、nuclear factor NF-κB,explore the relationship between different groups and time periods.Results:The expression of IL-6mRNAin6hour in group HMGB1+LPS(2.637±1.073)was significantly higher than that of LPS group(0.376±0.156); in groupHMGB1+LPS, the expression o TNF-α in8hour was916.52±38.31, IL-1was 1396.47±135.08, both were higher than group LPS, which was490.60±87.70to751.36±161.42respectively (P <0.05). Group LPS+HMGB1+TM-N compared withgroup LPS+HMGB1, in8hour the amount of TNF-α was307.21±39.98to916.52±38.31; IL-1was490.12±62.79to1396.47±135.08; in6hour IL-6mRNAwas0.318±0.216to2.637±1.073respectively, The former were less than the latter(P<0.05~0.01), And in2hour TM-N can restrain the NF-κB’s expression indused bygroup LPS+HMGB1, inhibition rate reached to81%(P <0.05). Group LPS+TM-Ncompared with group LPS, in8hour the amount of TNF-α was269.59±34.27to490.60±87.70, IL-1was427.37±108.68to751.36±161.42, in6hour IL-6mRNAwas0.265±0.115to1.275±0.156respectively, The former were less than the latter(P<0.05~0.01), And in2hour TM-N can restrain the NF-κB’s expression in groupLPS, inhibition rate reached to70%(P <0.05).Conclusions:1. HMGB1can enlarge inflammatory effects of LPS significantly2. TM-N can inhibit inflammatory induced both by LPS or LPS+HMGB1remarkablely.
Keywords/Search Tags:High mobility group box1protein (HMGB1), lipopolysaccharide (LPS), RAW264.7cell, thrombomodulin, N-terminal domain of TM(TM-N)
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